Evaluation of TMPRSS2-ERG Fusion Protein in Prostate Cancer Pathogenesis across Continents.
Rhonda Henshall-Powell, Charlie Yu, Ryan Bremer, Isabell A Sesterhenn, David Tacha. Biocare Medical, Concord, CA; AFIP, Washington, DC
Background: The incidence of prostate cancer is 30-50 times more prevalent in North American vs. Asian populations. Chromosomal translocations involving ETS transcription factors, such as ERG and ETV1, are frequent events in human prostate cancer pathogenesis. In particular, the TMPRSS2-ERG fusion gene was discovered to be the most frequent proto-oncogene present in 45-65% (North American) and 15-20% (Asian) of prostate cancers. The TMPRSS2-ERG fusion is associated with a more aggressive phenotype. Given the ease of performing IHC vs. FISH, ERG protein expression in FFPE tissue may be an extremely useful tool for the molecular subtyping of prostate cancer. This study evaluated the sensitivity and specificity of a mouse ERG mAb on human prostate tissues; comparing North American and Asian cases. A wide variety of normal and neoplastic tissues were tested to establish specificity.
Design: Tissue microarrays (TMA's) of human prostate adenocarcinoma (Grades 1-4 and Gleason Scores 2-10), normal prostate and other normal and neoplastic tissues were analyzed. TMA's were processed according to standard IHC protocols. Samples were incubated with mouse anti-ERG mAb for 30mins followed by chromogenic visualization (DAB-HRP).
Results: Only 19% (32/169) of tissues from patients of Asian descent showed high expression of ERG compared to 45% (15/33) of North American prostate TMA's. Gleason Score or tumor grade were not dependent upon ERG expression. 744 normal and neoplastic tissues analyzed: only 0.4% (3/744) showed positive staining for ERG: one each of a T-Cell Lymphoma, B-Cell Lymphoma and Melanoma; thereby demonstrating 99.6% specificity for prostate tissues.
Conclusions: High specificity of TMPRSS2-ERG expression (99.6%) in prostate cancer tissue was demonstrated with this mAb by examining normal and neoplastic tissues. ERG expression was independent of Gleason Score or tumor grade. The frequency of ERG expression was higher in North American vs. Asian patients, correlating to a higher incidence of prostate cancer in North American populations. Considering the association of TMPRSS2: ERG rearrangement with a more aggressive phenotype and a 96.5% correlation between ERG-positive PIN and ERG-positive carcinoma, the evaluation of ERG expression may be a valuable diagnostic tool.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 99, Monday Afternoon